The aim of the research project is to study in biochemical and morphological terms the mechanisms of fracture healing and to devise means to control the process. Fracture callus calcification is a process of tissue differentiation which can be followed by temporal changes of its enzyme and matrix components. We plan to induce fractures in the tibia of rabbits and sequentially at different stages of callus maturation study its biochemical characteristics in two separate systems (a) in vivo (b) in vitro along the following lines: a. Glycogen and glucose metabolism. b. Aerobic and anaerobic metabolism. c. Biosynthesis and metabolism of mitochondria. d. Extracellular vesicles and their role in transport. e. Distribution of lipids. f. Intra- and extracellular location of key enzymes and metabolities. g. Membrane permeability for various ions. The role of two modulators i.e. hormones and oxygen, known to exert significant effects on cartilage differentiation will be assessed by their influence on the above systems. It is hoped that from information gained by these means can then be used to control fracture healing, prevent pseudarthrosis, and induce calcification and union of pseudarthroses once they have already formed.